Tetrabenazine (TBZ) has a chemical structure represented by the following Formula 1, and the chemical name thereof is 1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-3-(2-methoxypropyl)-2H-benzo(a)quinolizin-2-one.

Further, dihydrotetrabenazine (DTBZ) is a metabolite of tetrabenazine (TBZ) and a product produced by reducing a 2-keto group of tetrabenazine, and has a chemical structure represented by the following Formula 2. The chemical name thereof is 2-hydroxy-3-(2-methoxypropyl)-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-benzo(a)quinolizine.

Tetrabenazine (TBZ) and dihydrotetrabenazine (DTBZ) are used as a therapeutic agent for neuropathy, mental disorder and the like by selectively binding to vesicular monoamine transporter-2 (VMAT2) [Jankovic et al., Am. J. Psychiatry. (1999) August; 156(8):1279-81 and Jankovic et al., Neurology (1997) February; 48(2):358-62]. Tetrabenazine (TBZ) was first synthesized in 1956, approved as a therapeutic medicine for neural diseases, mental diseases and the like in Finland, the Netherlands, Switzerland, England and the like, approved by the FDA in 2008, and has been currently used as a therapeutic agent for chorea symptoms of Huntington's disease. TBZ derivatives have been currently used as an imaging agent and a biomarker probe for diabetes and the like.
Representative methods for preparing tetrabenazine (TBZ), which have been recently know, are performed by using an addition reaction of non-symmetric malonate under a palladium catalyst [J. Org. Chem. 2009, 74, 4001]. That is, dihydroisoquinoline which is a starting material was introduced into malonate by using a palladium catalyst and (S)-DM-binap, and then was subjected to a reaction process including a total of 9 steps, such as Krapcho method and the like, to prepare a target compound.
As another preparation method of tetrabenazine (TBZ), dihydroisoquinoline which is a starting material was subjected to a reaction process including a total of 7 steps including a non-symmetric allylation reaction, a stereoselective enol-etherification reaction, an aza-Claisen rearrangement reaction and a transannulation reaction under an acid catalyst to prepare tetrabenazine [Chem-A. Eur. J. 2010, 16, 4623].
As studied above, tetrabenazine (TBZ) and dihydrotetrabenazine (DTBZ) which is a metabolite thereof are compounds which have high medical use values, and an industrial mass production thereof is required, but preparation methods released until now include multi-step processes and thus have limitations for commercial use.